Elevated Expression of Two Circulating LncRNAs Predicts Poor Prognosis for Acute Cerebral Infarction

Poor prognosis for acute cerebral infarction (ACI) was suggested to be predicted using the high expression of some novel molecular markers, for example long non-coding RNAs (lncRNAs). Differentially expressed lncRNAs in peripheral whole blood from the ACI patients and healthy volunteers(HVT) were identified using microarray and further verified by qRT-PCR. The clinical outcome evaluated by 3-month modified Rankin Score (mRS), stroke stratification classified by OCSP criteria, and the expression characteristics of specific lncRNAs were analyzed in ACI patients. Among 5686 differentially expressed lncRNAs screened out by the microarray, nine were verified by qRT-PCR. Particularly, the expression of NR_120420 and lnc-GCH1-2:3 in the ACI group were significantly higher than the HVT group. ROC analysis showed that the sensitivity and specificity of NR_120420 were 85.7% and 84.6% in patients with total anterior circulation infarction (TACI) respectively(area under curve，AUC=0.861), while the sensitivity and specificity of lnc-GCH1-2:3 were 85.7% and 82.1% in patients with TACI respectively(AUC=0.802). Multivariate logistic regression showed that NR_120420 was a significantly independent diagnostic factor for ACI. The elevated expression levels of NR_120420 and lnc-GCH1-2:3 were associated with the TACI stroke classification and the poor prognosis of ACI. Our study clearly illustrated that the elevated expression levels of circulating NR_120420 and lnc-GCH1-2:3 could predict the TACI stroke classification with high sensitivity and specificity and the poor prognosis of patients with ACI. Peripheral whole blood from patients with acute cerebral infarction (ACI) (n=6) and healthy controls (HVT) (n=3) were screened by microarray to find differentially expressed lncRNAs.Time duration from stroke onset to admission was less than 6 hours.

已有研究表明，可通过部分新型分子标志物的高表达预测急性脑梗死（acute cerebral infarction, ACI）的不良预后，例如长链非编码RNA（long non-coding RNAs, lncRNAs）。本研究通过微阵列（microarray）筛选急性脑梗死患者与健康志愿者（healthy volunteers, HVT）外周全血中的差异表达lncRNAs，并采用qRT-PCR对筛选得到的分子进行验证。随后，针对急性脑梗死患者的临床结局（以3个月改良Rankin量表（modified Rankin Score, mRS）评估）、基于OCSP分型的卒中分层以及特异性lncRNAs的表达特征展开分析。

在微阵列筛选得到的5686个差异表达lncRNAs中，有9个经qRT-PCR验证属实。尤为关键的是，NR_120420与lnc-GCH1-2:3在急性脑梗死组中的表达水平显著高于健康志愿者组。

受试者工作特征曲线（receiver operating characteristic curve, ROC）分析结果显示：在总前循环梗死（total anterior circulation infarction, TACI）患者中，NR_120420的灵敏度与特异度分别为85.7%与84.6%（曲线下面积（area under curve, AUC）=0.861）；而lnc-GCH1-2:3的灵敏度与特异度分别为85.7%与82.1%（AUC=0.802）。

多元逻辑回归（multivariate logistic regression）分析表明，NR_120420是急性脑梗死的独立诊断相关因素。NR_120420与lnc-GCH1-2:3的表达升高与TACI卒中分型及急性脑梗死不良预后显著相关。

本研究明确证实，循环中NR_120420与lnc-GCH1-2:3的高表达可实现对TACI卒中分型的高灵敏度、高特异度预测，同时可有效预测急性脑梗死患者的不良预后。

本研究通过微阵列筛选差异表达lncRNAs时，纳入了6例急性脑梗死患者与3例健康对照的外周全血样本，所有受试者从卒中发病至入院的时间均小于6小时。